Hydrochloric Acid → 6-(3,5-difluorophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one

HRID 401025Notes

Reaction equation

HRID 401025 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([N+:30]([O-:32])=[O:31])[C:28]=1[OH:29])[CH:24]=O)[CH3:19].[NH2:33][C:34]([NH2:36])=[O:35].Cl>C(O)C>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[NH:36][C:34](=[O:35])[NH:33][CH:24]([C:23]3[CH:26]=[C:27]([N+:30]([O-:32])=[O:31])[C:28]([OH:29])=[C:21]([O:20][CH2:18][CH3:19])[CH:22]=3)[C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 27583193',5'-Difluoro-2-phenylacetophenone2×

Product 1

HCID 569613476-(3,5-difluorophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-oneYield 19.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-(3,5-difluorophenyl)-2-phenylethanone (Intermediate 18) (100 mg, 0.43 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (84.9 mg, 0.43 mmol), and urea (78.6 mg, 1.29 mmol) in 5 mL of ethanol was added 0.2 mL of concentrated HCl, and the mixture was refluxed for 2 days. After the solvent was removed under reduced pressure, the residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.) to give Compound 46 (40 mg, yield 19.9%). 1H NMR (DMSO-d6 400 MHz) δ 10.27 (s, 1H), 8.81 (s, 1H), 7.56 (s, 1H), 7.41 (s, 1H), 7.31 (m, 2H), 7.14 (s, 1H), 7.11-6.99 (m, 4H), 6.86 (d, J=7.2 Hz, 2H), 5.24 (s, 1H), 4.04 (m, 2H), 1.32 (t, J=7.2 Hz, 3H); MS (ESI): m/z 468.0 [M+1]+.

Workup

  1. temperaturethe mixture was refluxed for 2 days
  2. customAfter the solvent was removed under reduced pressure
  3. customthe residue was purified by reverse-phase preparatory HPLC (26-53% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 15 min.)

Sources & evidence

ORD record
ord-6e9bf2c79f6d4515881856947ee0bf18
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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